The organization of transmitter identifiable neurons will be investigated in two model systems crucial to control of colon motility. These are the inferior mesenteric ganglion (IMG) and the functionally associated myenteric plexuses of the colon. Neuronal types, synaptic connections and basic circuits will be subjected to detailed study using catecholamine fluorescence with computer assisted image analysis, electronmicroscopy with five- hydroxydopamine labelling, and immunocytochemistry coupled with electron microscopy. Immunocytochemistry will be used in combination with fluorescent dye tracing to trace substance P and vasoactiveintestinal; polypeptide (VIP) connections between the myenteric plexus, the IMG and the dorsal root ganglia. 1. Small intensely fluorescent (SIF) cells in the guinea pig IMG will be studied using fluorescence mircroscopic (FM) and electron microscopic (EM) techniques to investigate SIF cells as a basis for understanding their role(s) in intraganglionic modulation (e.g. is their preferred status as interneurons, associative neurons, or paraneurons; or are they diverse?) 2. In the myenteric plexus of the guinea pig colon, axons and terminals of noradrenergic (NA) neurons as well as their interactions with enteric neurons and their processes will be examined in detail by EM to locate site(s) of adrenergic action. Another purpose is to identify (and compare with the IMG) the cellular mechanisms by which NA release occurs in the colon (is it released by specialized (synaptic) or unspecialized contacts; or directly into extracellular space, etc.?). 3. For studying transmitter-specific links between colon and ganglia, fluorescent dye (single and double) retrograde tracing techniques combined with light microscopic immunocytochemistry will be used to test the hypotheses that substance P and VIP fibers in guinea pig IMG are (a) collaterals of peripheral sensory fibers from the colon or (b) visceral afferents originating from the colon. EM immunocytochemistry will be used to analyze and compare types and distribution of interactions made by SP and VIP fibers with PGNs and/or other neural elements in the IMG. The IMG and enteric nerves represent a synergic program for using greatly enriched transmitter technology to provide an anatomical substrate. This will strengthen and expand physiological and pharmacological opportunities to solve problems in both normal and pathological gastroenterology.